Despite the tremendous inter-individual variability in the respond to environmental toxins, the investigators simply do not understand why certain people develop disease when challenged with environmental agents and others remain healthy. Yet, there is emerging consensus that many of the complex (and prevalent) diseases that humans develop occur as a result of multiple biologically unique gene-gene and gene-environment interactions. The recent advances in human and molecular genetics has provided an unparalleled opportunity to understand how genes and genetic changes interact with environmental stimuli to either preserve health or cause disease. The theme of this Center is to use gene expression profiling to understand the effect of environmental stresses on human health. This will be accomplished by establishing an interdisciplinary Center that supports the use of complementary biologic systems (humans, mice, zebrafish and worms) to investigate the role of genetic susceptibility in the pathogenic response to specific types of environmental stress (bacteria, malnutrition, and metals). This approach will enable the investigators to develop and investigate environmental models of human disease that represent biologically unique gene-environment- pathophysiological phenotypes. Microarray analyses will be used to comprehensively evaluate the biological response to environmental stress and to identify pathogenic mechanisms that are relevant to innate immunity, neural tube defects, and transition metal toxicity. The end result is a broad based yet highly integrated program that has the potential to make a number of novel, related observations. The overall hypothesis unifying this research program is that gene expression profiling will identify genes and pathogenic processes that are critical to human environmental health and disease. In aggregates the coupled scientific findings from the proposed Program will substantially enhance our understanding of environmental toxicology and genomics.